Purpose: To explore the effectiveness of different anti-seizure medications in preventing early and late post-traumatic epilepsy (PTE). The efficacy, treatment-related side-effects, and mortality of the different treatments were compared using a ranking model to identify the optimal treatment. Methods: A comprehensive literature search was performed using Pubmed, Medline, Embase, and Cochrane library databases. All relevant published articles up to 10 March 2022 were evaluated. The quality of the extracted data was assessed using either the Cochrane risk of bias tool or the Newcastle-Ottawa scale. The primary outcome measures were early or late post-traumatic seizures. The secondary outcome measures were mortality, treatmentrelated adverse effects, length of hospital stay, and length of stay within the intensive care unit (ICU).Results: A total of seven randomized controlled trials and 18 non-randomized controlled trials were included in this network meta-analysis. The trials included six interventions: Phenytoin (PHT)+phenobarbital (PB), levetiracetam (LEV), PHT, PHT-LEV, lacosamide (LCM), and valproate (VPA). All interventions except VPA significantly reduced the rate of early PTE in TBI patients compared with the placebo. Seven studies reported the impact of four treatments (PHT + PB, LEV, PHT, VPA) on late seizures and showed a significant reduction in the incidence of late seizures in patients with TBI